PMID- 28949956 OWN - NLM STAT- MEDLINE DCOM- 20171205 LR - 20210102 IS - 1532-1827 (Electronic) IS - 0007-0920 (Print) IS - 0007-0920 (Linking) VI - 117 IP - 11 DP - 2017 Nov 21 TI - A positive-feedback loop between tumour infiltrating activated Treg cells and type 2-skewed macrophages is essential for progression of laryngeal squamous cell carcinoma. PG - 1631-1643 LID - 10.1038/bjc.2017.329 [doi] AB - BACKGROUND: Foxp3(+) regulatory T (Treg) cells and M2 macrophages are associated with increased tumour progression. However, the interaction between Treg cells and M2 macrophages remains unclear. METHODS: The expression of FoxP3 and CD163 was detected by immunohistochemistry in 65 cases of laryngeal squamous cell carcinoma (LSCC). In vitro, the generation of activated Treg (aTreg) cells and M2 macrophages by interactions with their precursor cells were analysed by flow cytometry and ELISA. In vivo, the antitumour effects were assessed by combined targeting aTreg cells and M2 macrophages, and intratumoural immunocytes were analysed by flow cytometry. RESULTS: In LSCC tissue, accumulation of aTreg cells and M2 macrophages predicted a poor prognosis and were positively associated with each other. In vitro, aTreg cells were induced from CD4(+)CD25(-) T cells by cancer cell-activated M2-like macrophages. Consequently, these aTreg cells skewed the differentiation of monocytes towards an M2-like phenotype, thereby forming a positive-feedback loop. Combined targeting aTreg cells and M2 macrophages led to potent antitumour immunity in vivo. CONCLUSIONS: The positive-feedback loop between aTreg cells and M2 macrophages is essential to maintain or promote immunosuppression in the tumour microenvironment and may be a potential therapeutic target to inhibit tumour progression. FAU - Sun, Wei AU - Sun W AD - Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China. AD - Institute of Otorhinolaryngology Head and Neck Surgery, Sun Yat-sen University, Guangzhou 510080, China. FAU - Wei, Fan-Qin AU - Wei FQ AD - Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China. AD - Institute of Otorhinolaryngology Head and Neck Surgery, Sun Yat-sen University, Guangzhou 510080, China. AD - Department of Otorhinolaryngology Head and Neck Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510655, China. FAU - Li, Wei-Jin AU - Li WJ AD - Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China. AD - Institute of Otorhinolaryngology Head and Neck Surgery, Sun Yat-sen University, Guangzhou 510080, China. FAU - Wei, Jia-Wei AU - Wei JW AD - Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China. AD - Institute of Otorhinolaryngology Head and Neck Surgery, Sun Yat-sen University, Guangzhou 510080, China. FAU - Zhong, Hua AU - Zhong H AD - Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China. AD - Institute of Otorhinolaryngology Head and Neck Surgery, Sun Yat-sen University, Guangzhou 510080, China. FAU - Wen, Yi-Hui AU - Wen YH AD - Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China. AD - Institute of Otorhinolaryngology Head and Neck Surgery, Sun Yat-sen University, Guangzhou 510080, China. FAU - Lei, Wen-Bin AU - Lei WB AD - Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China. AD - Institute of Otorhinolaryngology Head and Neck Surgery, Sun Yat-sen University, Guangzhou 510080, China. FAU - Chen, Lin AU - Chen L AD - Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China. AD - Institute of Otorhinolaryngology Head and Neck Surgery, Sun Yat-sen University, Guangzhou 510080, China. FAU - Li, Hang AU - Li H AD - Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China. AD - Institute of Otorhinolaryngology Head and Neck Surgery, Sun Yat-sen University, Guangzhou 510080, China. FAU - Lin, Han-Qing AU - Lin HQ AD - Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China. AD - Institute of Otorhinolaryngology Head and Neck Surgery, Sun Yat-sen University, Guangzhou 510080, China. FAU - Iqbal, Muhammad AU - Iqbal M AD - Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China. AD - Institute of Otorhinolaryngology Head and Neck Surgery, Sun Yat-sen University, Guangzhou 510080, China. FAU - Wen, Wei-Ping AU - Wen WP AD - Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China. AD - Institute of Otorhinolaryngology Head and Neck Surgery, Sun Yat-sen University, Guangzhou 510080, China. LA - eng PT - Journal Article DEP - 20170926 PL - England TA - Br J Cancer JT - British journal of cancer JID - 0370635 SB - IM MH - Animals MH - Carcinoma, Squamous Cell/*immunology MH - Cell Differentiation MH - Cell Line, Tumor MH - Disease Progression MH - Feedback, Physiological MH - Head and Neck Neoplasms/*immunology MH - Humans MH - Immune Tolerance MH - Laryngeal Neoplasms/*immunology MH - Lymphocytes, Tumor-Infiltrating/*immunology MH - Macrophages/*physiology MH - Male MH - Mice MH - Mice, Inbred C3H MH - Squamous Cell Carcinoma of Head and Neck MH - T-Lymphocytes, Regulatory/*immunology PMC - PMC5729431 COIS- The authors declare no conflict of interest. EDAT- 2017/09/28 06:00 MHDA- 2017/12/06 06:00 PMCR- 2018/11/21 CRDT- 2017/09/27 06:00 PHST- 2017/05/21 00:00 [received] PHST- 2017/08/08 00:00 [revised] PHST- 2017/08/24 00:00 [accepted] PHST- 2017/09/28 06:00 [pubmed] PHST- 2017/12/06 06:00 [medline] PHST- 2017/09/27 06:00 [entrez] PHST- 2018/11/21 00:00 [pmc-release] AID - bjc2017329 [pii] AID - 10.1038/bjc.2017.329 [doi] PST - ppublish SO - Br J Cancer. 2017 Nov 21;117(11):1631-1643. doi: 10.1038/bjc.2017.329. Epub 2017 Sep 26.